Department of Biological Sciences, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4, Canada.
Seidman Cancer Center, University Hospitals, 11100 Euclid Ave, Cleveland, OH 44106, USA.
Genes (Basel). 2019 Jan 9;10(1):34. doi: 10.3390/genes10010034.
The diagnostic and therapeutic agent gallium offers multiple clinical and commercial uses including the treatment of cancer and the localization of tumors, among others. Further, this metal has been proven to be an effective antimicrobial agent against a number of microbes. Despite the latter, the fundamental mechanisms of gallium action have yet to be fully identified and understood. To further the development of this antimicrobial, it is imperative that we understand the mechanisms by which gallium interacts with cells. As a result, we screened the Keio mutant collection as a means of identifying the genes that are implicated in prolonged gallium toxicity or resistance and mapped their biological processes to their respective cellular system. We discovered that the deletion of genes functioning in response to oxidative stress, DNA or iron⁻sulfur cluster repair, and nucleotide biosynthesis were sensitive to gallium, while Ga resistance comprised of genes involved in iron/siderophore import, amino acid biosynthesis and cell envelope maintenance. Altogether, our explanations of these findings offer further insight into the mechanisms of gallium toxicity and resistance in .
诊断和治疗剂镓具有多种临床和商业用途，包括治疗癌症和肿瘤定位等。此外，事实证明，这种金属是对抗多种微生物的有效抗菌剂。尽管如此，镓作用的基本机制尚未完全确定和理解。为了进一步开发这种抗菌剂，我们必须了解镓与细胞相互作用的机制。因此，我们筛选了 Keio 突变体文库，以确定与镓毒性延长或耐药性相关的基因，并将它们的生物过程映射到相应的细胞系统。我们发现，对氧化应激、DNA 或铁硫簇修复以及核苷酸生物合成有反应的基因的缺失对镓敏感，而 Ga 耐药性则由涉及铁/铁载体摄取、氨基酸生物合成和细胞包膜维持的基因组成。总之，我们对这些发现的解释进一步深入了解了 在 中的镓毒性和耐药性的机制。
